Ulcerative ColitisPhase 3NCT01805791
A Phase III Trial of HMPL-004 in Patients With Mild to Moderate Active Ulcerative Colitis
A Phase 3 study testing HMPL-004 1800 mg/day and HMPL-004 2400 mg/day in people with Ulcerative Colitis, run by Hutchison Medipharma Limited at 1 site in United States.
Trial summary
A placebo controlled study of two doses of HMPL-004 in patients with active mild to moderate ulcerative colitis (UC), with a modified Mayo Score 4-10 and an endoscopy subscore of 2-3, taking mesalamine (or equivalent) as a concomitant medication. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Ulcerative Colitis
- What is being tested?
- HMPL-004 1800 mg/day and HMPL-004 2400 mg/day
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 201 participants
- Where
- 1 siteUnited States
- Study dates
- Mar 2013to Oct 2014
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients must be currently receiving mesalamine ≥ 2.4 g/day (or the equivalent) for at least 6 weeks prior to randomization and on a stable dosage for at least 2 weeks prior to entering the screening phase of the study to ensure a stable dose is established at least 2 weeks prior to the endoscopic procedures.
- Have active mild to moderate ulcerative colitis defined by a modified Mayo Score 4-10, and with endoscopy score activity of 2-3 points confirmed by centrally read colonoscopy (within 2 weeks prior to randomization.
- Minimum modified Mayo endoscopy score of >2 at the time of study colonoscopy.
- Age ≥ 18 years.
- Patients have no prior exposure to HMPL-004.
- Have adequate renal, hepatic and bone marrow function (see exclusion criteria).
- All fertile male and female subjects must agree to use one of the following types of contraception: abstinence, intrauterine device, implantable progesterone device, and progesterone intramuscular injection, oral contraceptive which has been started at least one month prior to visit one and continues for the duration of the trial, contraceptive patch, or condom with spermicide.
- Show evidence of a personally signed and dated informed consent document indicating that the patient (or legally acceptable representative) has been informed of all pertinent aspects of the trial
Who cannot join
- Subjects with intolerance or adverse reactions to mesalamine (or equivalent medications).
- Diagnosed with Crohn's Disease or with lesions such as fistulas or granulomas on biopsy noted either in history or at baseline endoscope, which would be suspicious for Crohn's disease, or with a diagnosis of indeterminate colitis. Subjects with Primary Sclerosing Cholangitis (PSC) are excluded..
- Severe disease with an ulcerative colitis modified Mayo Clinic score above 10 points at baseline.
- Positive stool test for pathogens for sample taken within the previous 2 weeks prior to study entry.
- Active Clostridium difficile (C. diff) infection.
- Use of Inflammatory Bowel Disease related herbal supplements including but not limited to supplements containing andrographis and probiotics two weeks prior to study entry or during the study.
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- Toxic megacolon or toxic colitis.
- Probable requirement for intestinal surgery within 12 weeks after the start of study medication.
- Receiving oral or rectal steroids within 1 month prior to study entry.
- Receiving rectal mesalamine within one week prior to study entry.
- Receiving azathioprine, 6-mercaptopurine, methotrexate, tacrolimus, cyclosporine, or other immunosuppressive therapy at the time of screening or within the preceding 6 weeks.
- Receiving anti-tumor necrosis factor-α agents such as infliximab, adalimumab, golimumab, or certolizumab pegol at the time of screening or within the preceding 8 weeks.
- Receiving other investigational drugs or biologics within 1 month or five half lives.
- Receiving antibiotics within 2 weeks of study entry.
- Hemoglobin concentration < 9 g/dl.
- White blood cell count (WBC) below 3,000/cmm, or platelets below 100,000/cmm.
- Serum glutamate oxaloacetate transaminase (SGOT), serum glutamate pyruvate transaminase (SGPT), alkaline phosphatase >2.5 upper limit of normal.
- Serum creatinine >1.5 times upper limit of normal.
- Significant concurrent medical diseases including: active peptic ulcer disease; uncompensated congestive heart disease; myocardial infarction within the last 12 months; unstable angina pectoris; uncontrolled hypertension; pulmonary disease requiring oxygen therapy.
- Chronic Hepatitis B or any history of Hepatitis C.
- Previous colonic surgery except for simple polypectomy or appendectomy. .
- History of cancer within the last 5 years other than resected cutaneous basal and squamous cell carcinomas, and in situ cervical cancer.
- Patients with a history of or concurrent colonic dysplasia associated with UC, except those with completely excised sporadic colorectal polyps.
- Women who are pregnant or breast feeding.
- Patients known to be seropositive for HIV, or who have had an AIDS defining illness, or a known immunodeficiency disorder.
- Patients with a history of tuberculosis or exposure to tuberculosis, or a history of a chest X-ray suspicious for tuberculosis, unless confirmed to be purified protein derivative (PPD) skin test negative or latent tuberculosis that has been previously treated.
- History of alcohol or drug abuse that would interfere with the ability to be compliant with the study procedure.
- Known allergy to plants of the Acanthaceae family.
- Unwillingness to participate in the study.
- Any underlying medical condition that in the Investigator's opinion will make the administration of study drug hazardous to the patient or would obscure the interpretation of adverse events.
Trial locations and contacts
1 site in 1 country.
United States1 site
Clinical Research Management, Inc
Agawam, Massachusetts, 01001
About this study
Official title: A Phase III, Randomized, Multi-Centre, Double-Blind, Placebo-Controlled Trial of HMPL-004 in Patients With Mild to Moderate Active Ulcerative Colitis
A placebo controlled study of two doses of HMPL-004 in patients with active mild to moderate ulcerative colitis (UC), with a modified Mayo Score 4-10 and an endoscopy subscore of 2-3, taking mesalamine (or equivalent) as a concomitant medication.
The objective is to evaluate the efficacy and safety of HMPL-004 with mesalamine (mesalamine treatment failures). Efficacy will be measured by a comparison of the proportion of patients in each treatment group attaining clinical remission at Week 8 as compared to placebo.
Read the detailed description
This Phase III study of HMPL-004 was to enroll approximately 420 subjects with active mild to moderate ulcerative colitis (UC; modified Mayo Score 4-10 and endoscopy score of 2-3). The trial included male and female subjects aged 18 or older. Subjects were currently receiving ≥2.4 g/day mesalamine or equivalent, provided they had taken 5-aminosalicylate (ASA; i.e., mesalamine) at a dose ≥2.4 g/day for at least 6 weeks prior to randomization and were on a stable dosage for at least 2 weeks prior to entering the screening phase of the study.
Qualifying subjects who entered into this study received 3 daily doses of oral HMPL 004 tablets or placebo for 56 days (8 weeks). There were 3 arms in this study consisting of placebo, HMPL-004 600 mg three times a day (TID) or 800 mg TID. Approximately 420 subjects were to be randomized 1:1:1 to one of these 3 arms, stratified by country/region in up to 150 clinical centers in North America, Europe, and Asia.
- Conditions
- Ulcerative Colitis
- Being tested
- HMPL-004 1800 mg/day, Placebo, HMPL-004 2400 mg/day
- Keywords
- Ulcerative Colitis,, UC, Patients, active, mild, moderate
- Medical subject headings
- Colitis, Ulcerative, Motor Activity, Lymphoma, Follicular
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
HMPL-004 1800 mg/dayDrug
Also called Chuan xinlian
Subjects randomized to the arm of HMPL-004 1800 mg/day will receive HMPL-004 600 mg TID (total dose 1800 mg/day) for 56 days (8 weeks).
PlaceboDrug
Subjects randomized to the arm of Placebo will receive matching Placebo three times daily for 56 days (8 weeks).
HMPL-004 2400 mg/dayDrug
Also called Chuan xinlian
Subjects randomized to the arm of HMPL-004 2400 mg/day will receive HMPL-004 800 mg TID (total dose 2400 mg/day) for 56 days (8 weeks).
| Study group | Role | What they receive |
|---|---|---|
| Placebo | Placebo comparator | Placebo, oral tablets, three times a day Receives: Drug: Placebo |
| HMPL-004 1800 mg/day | Experimental | 1 600 mg HMPL-004 tablet, 2x400 mg placebo tablets taken 3 times a day Receives: Drug: HMPL-004 1800 mg/day |
| HMPL-004 2400 mg/day | Experimental | 2 x 400 mg HMPL tablets, 1 x 600 mg placebo tablet, taken 3 times per day Receives: Drug: HMPL-004 2400 mg/day |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percentage of Subjects With a Clinical Remission at Week 8
Clinical remission was defined as a total Mayo Score of ≤2 points with no individual sub-score >1 point and rectal bleeding score = 0.
Measured: 8 weeks
Secondary outcomes (2)
The Proportion of Subjects With Clinical Response at Week 8
Clinical response was defined as a decrease in a modified Mayo Score from baseline by ≥3 points and ≥30% decrease in the modified Mayo Score, along with either a decrease in the rectal bleeding score ≥1 or an absolute rectal bleeding score ≤1.
Measured: 8 weeks
The Proportion of Subjects With Mucosal Healing at Week 8
Mucosal healing was defined as having normal or inactive disease using a modified Mayo Score to determine if the decrease in the modified Mayo endoscopy sub-score from baseline was ≥1 in at least 1 segment and had an absolute score ≤1 in all segments.
Measured: 8 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Mar 2013 (estimated)
- Study startMar 2013
- Primary completionOct 2014
- Study completionOct 2014
Why it stopped: Interim futility analysis results
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Ulcerative ColitisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 201 participants (actual)
Sponsor and investigators
- Lead sponsor
- Hutchison Medipharma Limited
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Rongjun Liu, MD, Study director, Hutchison Medipharma Limited
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01805791
- Sponsor's protocol ID
- HMPL-004-03
- Status last verified
- Jul 2018
- First submitted
- 4 Mar 2013
- Last updated
- 2 Jan 2020
- Results posted
- Yes, on ClinicalTrials.gov
Study at a glance
From the registry record, last updated by the sponsor on 2 Jan 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase III, Randomized, Multi-Centre, Double-Blind, Placebo-Controlled Trial of HMPL-004 in Patients With Mild to Moderate Active Ulcerative Colitis
- ClinicalTrials.gov ID
- NCT01805791
- Acronym / sponsor ID
- HMPL-004-03
- Conditions
- Ulcerative Colitis
- Keywords
- Ulcerative Colitis,, UC, Patients, active, mild, moderate
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Interim futility analysis results
- Enrolment
- 201 participants (actual)
- Lead sponsor
- Hutchison Medipharma LimitedIndustry (pharma, biotech, devices)
- Study start
- Mar 2013 (actual)
- Primary completion
- Oct 2014 (actual)
- Study completion
- Oct 2014 (actual)
- First posted
- 6 Mar 2013 (estimated)
- Results
- Posted 2 Jan 2020
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
A placebo controlled study of two doses of HMPL-004 in patients with active mild to moderate ulcerative colitis (UC), with a modified Mayo Score 4-10 and an endoscopy subscore of 2-3, taking mesalamine (or equivalent) as a concomitant medication.
The objective is to evaluate the efficacy and safety of HMPL-004 with mesalamine (mesalamine treatment failures). Efficacy will be measured by a comparison of the proportion of patients in each treatment group attaining clinical remission at Week 8 as compared to placebo.
Detailed description
This Phase III study of HMPL-004 was to enroll approximately 420 subjects with active mild to moderate ulcerative colitis (UC; modified Mayo Score 4-10 and endoscopy score of 2-3). The trial included male and female subjects aged 18 or older. Subjects were currently receiving ≥2.4 g/day mesalamine or equivalent, provided they had taken 5-aminosalicylate (ASA; i.e., mesalamine) at a dose ≥2.4 g/day for at least 6 weeks prior to randomization and were on a stable dosage for at least 2 weeks prior to entering the screening phase of the study.
Qualifying subjects who entered into this study received 3 daily doses of oral HMPL 004 tablets or placebo for 56 days (8 weeks). There were 3 arms in this study consisting of placebo, HMPL-004 600 mg three times a day (TID) or 800 mg TID. Approximately 420 subjects were to be randomized 1:1:1 to one of these 3 arms, stratified by country/region in up to 150 clinical centers in North America, Europe, and Asia.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Placebo | Placebo comparator | Drug: PlaceboPlacebo, oral tablets, three times a day |
| HMPL-004 1800 mg/day | Experimental | Drug: HMPL-004 1800 mg/day1 600 mg HMPL-004 tablet, 2x400 mg placebo tablets taken 3 times a day |
| HMPL-004 2400 mg/day | Experimental | Drug: HMPL-004 2400 mg/day2 x 400 mg HMPL tablets, 1 x 600 mg placebo tablet, taken 3 times per day |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- Patients must be currently receiving mesalamine ≥ 2.4 g/day (or the equivalent) for at least 6 weeks prior to randomization and on a stable dosage for at least 2 weeks prior to entering the screening phase of the study to ensure a stable dose is established at least 2 weeks prior to the endoscopic procedures.
- Have active mild to moderate ulcerative colitis defined by a modified Mayo Score 4-10, and with endoscopy score activity of 2-3 points confirmed by centrally read colonoscopy (within 2 weeks prior to randomization.
- Minimum modified Mayo endoscopy score of >2 at the time of study colonoscopy.
- Age ≥ 18 years.
- Patients have no prior exposure to HMPL-004.
Key exclusion criteria (30 listed)
- Subjects with intolerance or adverse reactions to mesalamine (or equivalent medications).
- Diagnosed with Crohn's Disease or with lesions such as fistulas or granulomas on biopsy noted either in history or at baseline endoscope, which would be suspicious for Crohn's disease, or with a diagnosis of indeterminate colitis. Subjects with Primary Sclerosing Cholangitis (PSC) are excluded..
- Severe disease with an ulcerative colitis modified Mayo Clinic score above 10 points at baseline.
- Positive stool test for pathogens for sample taken within the previous 2 weeks prior to study entry.
- Active Clostridium difficile (C. diff) infection.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| HMPL-004 1800 mg/dayAlso: Chuan xinlianSubjects randomized to the arm of HMPL-004 1800 mg/day will receive HMPL-004 600 mg TID (total dose 1800 mg/day) for 56 days (8 weeks). | Drug | HMPL-004 1800 mg/day |
| PlaceboSubjects randomized to the arm of Placebo will receive matching Placebo three times daily for 56 days (8 weeks). | Drug | Placebo |
| HMPL-004 2400 mg/dayAlso: Chuan xinlianSubjects randomized to the arm of HMPL-004 2400 mg/day will receive HMPL-004 800 mg TID (total dose 2400 mg/day) for 56 days (8 weeks). | Drug | HMPL-004 2400 mg/day |
Primary outcome
Percentage of Subjects With a Clinical Remission at Week 8
Time frame: 8 weeks
Clinical remission was defined as a total Mayo Score of ≤2 points with no individual sub-score >1 point and rectal bleeding score = 0.
2 secondary outcomes
The Proportion of Subjects With Clinical Response at Week 8
Time frame: 8 weeks
The Proportion of Subjects With Mucosal Healing at Week 8
Time frame: 8 weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Jan 2020.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Rongjun Liu, MD study director
Hutchison Medipharma Limited
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing HMPL-004 1800 mg/day and HMPL-004 2400 mg/day in people with Ulcerative Colitis, run by Hutchison Medipharma Limited at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 30 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 2 Jan 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 2 Jan 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Percentage of Subjects With a Clinical Remission at Week 8 (time frame: 8 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Jan 2020.